Family Medicine Board Review · Combined Sources: AAFP 2019/2024 + PGY4 Outpatient Anticoagulants Lecture
Anticoagulation — Complete High-Yield Summary
Merged and cross-checked from both your files: warfarin mechanism/dosing/monitoring, full DOAC dosing and interaction tables, LMWH/fondaparinux comparison, AFib stroke-risk scoring, bleeding-risk tools, major bleeding reversal protocols, and the complete perioperative bridging/hold/restart framework (now with the exact procedure-level tables).
Anticoagulant Classes & Targets
Vitamin K Antagonist
Warfarin — targets factors II, VII, IX, X (+ inhibits Protein C & S)
Factor Xa Inhibitors (DOACs)
Apixaban, rivaroxaban, edoxaban
Direct Thrombin Inhibitor (DOAC)
Dabigatran
Parenteral Xa/IIa Inhibitors
LMWH, UFH (inhibit factors Xa and IIa); fondaparinux (inhibits Xa only)
Pearl: warfarin is the only agent that also suppresses natural anticoagulants (Protein C/S) — this is unique to VKAs and is the mechanistic basis for its early paradoxical hypercoagulable window.
LMWH & Fondaparinux
- LMWH = parenteral anticoagulant, derived from unfractionated heparin
- Common agents: enoxaparin (Lovenox), dalteparin (Fragmin)
- Anticoagulant effect mainly via factor Xa inhibition; subcutaneous LMWH has predictable absorption/response
- Routine anti-Xa monitoring usually not needed (per ASH guidelines) — consider only if obese or renal impairment
- LMWH has similar bleeding risk but lower HIT risk than UFH — but still avoid in patients with prior HIT
| Drug/Dose | Renal Adjustment | Half-Life | Key Point |
|---|
| Enoxaparin 1mg/kg SC q12h or 1.5mg/kg SC q24h | 1mg/kg SC q24h if CrCl <30 | 3–6h | UFH may be preferred if high bleeding risk (short half-life, reversible) or CrCl <30 |
| Dalteparin 200 units/kg SC once daily | Use with caution + monitor anti-Xa if CrCl <30 | 3–5h | — |
| Fondaparinux (Arixtra) — weight-based: <50kg = 5mg; 50–100kg = 7.5mg; >100kg = 10mg SC daily | Caution CrCl 30–50; contraindicated if CrCl <30 | 18h (longest) | Not FDA-approved for HIT but used off-label; comparable efficacy/safety to LMWH; longer half-life = convenient daily dosing but less reversible |
Board trap: fondaparinux is contraindicated at CrCl <30 — stricter than enoxaparin's dose-reduction approach at the same cutoff. Its long 18-hour half-life is both an advantage (once-daily) and disadvantage (harder to reverse) perioperatively.
Vitamin K Antagonist (Warfarin)
Mechanism
- Inhibits vitamin K epoxide reductase (VKOR), blocking the cyclic regeneration of active vitamin K
- Result: ↓ activation of factors II, VII, IX, X AND ↓ anticoagulant proteins C & S
- Acts primarily in the liver
Paradoxical Hypercoagulability
Early therapy reduces Protein C & S faster than clotting factors → temporary increased clotting risk → requires bridging therapy (heparin/LMWH).
Delayed Effect
Full anticoagulant effect takes ~5 days — existing clotting factors remain in circulation with differing half-lives until cleared.
Exam pearl: the Protein C/S vs. factor II/VII/IX/X depletion-rate mismatch is the classic mechanistic explanation tested for both (1) why bridging is required and (2) rare complications like warfarin-induced skin necrosis.
Bridging Therapy
- Start heparin or LMWH with the VKA
- Continue for: at least 5 days AND until INR is therapeutic for ≥24 hours
- Target INR range depends on indication (and sometimes comorbidities)
Dosing Principles
- Standard initiation/maintenance: 5 mg/day
- Lower doses needed in: elderly, liver disease, poor nutrition, heart failure
- Factors that increase effect (↑ INR): diarrhea, fever, hyperthyroidism
Timing & Administration
- Take at the same time every day — evening dosing preferred, allowing same-day dose adjustment after INR results come back
INR Monitoring Schedule
- Baseline INR → follow-up after 2–3 doses
- Then: twice weekly → weekly → every other week → monthly
- Stable patients (≥3 months stable INR without dose change): monitor every 12 weeks (ACCP guideline)
Dose Adjustment Strategy
- If INR out of range: first exclude causes (diet, drugs, illness)
- Then adjust the TOTAL WEEKLY dose (not just one day's dose) by 5–20%
Board trap: warfarin dose adjustments should be made to the total weekly dose, not by arbitrarily changing a single day's tablet — a frequently tested practical dosing nuance.
Warfarin INR Goals by Indication
| Indication | Target INR (Range) |
|---|
| VTE treatment or prophylaxis | 2.5 (2–3) |
| Atrial fibrillation | 2.5 (2–3) |
| Mechanical mitral valve replacement | 3.0 (2.5–3.5) |
| Other valve replacements | 2.5 (2–3) |
| Antiphospholipid syndrome | 2.5 (2–3) |
Board trap: mechanical mitral valve is the ONE indication with a higher target INR (3.0, range 2.5–3.5) — every other listed indication targets the standard 2.5 (2–3). Mechanical aortic valves are typically also targeted around 2.5–3, but mitral position carries higher thrombotic risk, hence the higher target.
Managing Supratherapeutic INR (No Significant Bleeding)
| INR | Management | Vitamin K Dosing |
|---|
| Above goal, but <4.5 | Option 1: decrease/hold dose, ↑ monitoring, resume at lower dose once therapeutic.
Option 2: continue current dose if minimally elevated (≤0.5 above range) in a previously stable patient (grade 2C) | Not applicable |
| 4.5–10 | Hold next 1–2 doses, ↑ monitoring, resume at lower dose once therapeutic | No vitamin K (grade 2B) |
| >10 | Hold VKA, administer vitamin K (grade 2C), ↑ monitoring, repeat vitamin K as necessary, resume VKA at appropriate dose once therapeutic | 2.5–5 mg orally as one dose |
Exact numbers to memorize: oral vitamin K dose when indicated (INR >10, no bleeding) = 2.5–5 mg.
Warfarin Drug & Food Interactions
VKAs have numerous drug interactions. Interactions may ↑ anticoagulant effect (↑ INR → bleeding risk) or ↓ anticoagulant effect (↓ INR → thrombosis risk). Whenever starting/stopping an interacting drug: increase INR monitoring frequency.
Inhibitors of Warfarin Metabolism (may need LESS warfarin, ↑ INR)
Amiodarone, azole antifungals, Bactrim, cephalosporins, chemotherapy, diltiazem, doxycycline, fibrates, H2RAs, isoniazid, macrolides, metronidazole, protease inhibitors, quinolones
Inducers of Warfarin Metabolism (may need MORE warfarin, ↓ INR)
Azathioprine, barbiturates, carbamazepine, nafcillin, phenytoin, primidone, rifamycins
Increased Bleeding Risk (additive, not metabolic)
Aspirin, clopidogrel, fondaparinux, NSAIDs, prasugrel, ticagrelor, UFH/LMWH
Select Named Interactions (Table 4)
Antimicrobials: ciprofloxacin, clarithromycin, erythromycin, fluconazole, isoniazid, metronidazole, TMP-SMX, voriconazole
Cardiovascular: amiodarone, fluvastatin, gemfibrozil, lovastatin
Complementary/alternative: Devil's claw, garlic, ginkgo biloba
Miscellaneous: acute alcohol ingestion, phenytoin, sertraline
Board trap: amiodarone appears in BOTH the general "inhibitor" list and the specific cardiovascular interaction list — it is one of the single most important interactions to know, given how often it's co-prescribed with warfarin for atrial fibrillation. It increases warfarin's effect (requires dose reduction).
Food interaction: foods high in vitamin K (leafy greens — spinach, kale, broccoli) can reduce anticoagulant effect (↓ INR). Do NOT avoid vitamin K completely — instead, maintain consistent intake, since fluctuations (not the absolute amount) cause INR instability.
Warfarin Perioperative Teaching Case
Board-Style Question
A 67-year-old woman with hypertension and atrial fibrillation has taken warfarin for 10 years, hemodynamically stable with no AFib complications. Scheduled for
elective bladder sling surgery (high bleeding risk procedure). No other significant PMH. What is the most appropriate perioperative management of her warfarin?
Answer: Discontinue warfarin 5 days prior to surgery and restart 12–24 hours postoperatively (unless bleeding complication).
Reasoning: her CHA₂DS₂-VASc score is 3 — this places her at LOW thromboembolic risk (bridging is reserved for CHA₂DS₂-VASc ≥7 or CHADS₂ 5–6 in AFib). Since she is low-risk and her surgery carries high bleeding risk, no bridging is needed — simply hold warfarin 5 days before surgery and restart 12–24h after.
Exam pearl: the trap in this question is assuming all AFib-on-warfarin patients need bridging. Bridging is reserved for high thrombotic risk patients specifically (see the Indications for Bridging table below) — a "garden variety" AFib patient with a low-to-moderate CHA₂DS₂-VASc score does NOT need heparin bridging, just a hold-and-restart around surgery.
DOACs — Overview
- First-line therapy for VTE and stroke prevention in nonvalvular atrial fibrillation
- Common DOACs: dabigatran, rivaroxaban, apixaban, edoxaban (also betrixaban — VTE prophylaxis in acutely ill hospitalized patients)
Advantages Over VKAs
No routine INR monitoring · Minimal drug-food interaction · Rapid onset · Predictable pharmacokinetics · Fewer drug-drug interactions · Comparable or lower bleeding risk · Shorter half-life
Key Differences Among DOACs
Some require parenteral lead-in (
dabigatran, edoxaban — start after 5–10 days of parenteral anticoagulation)
Dosing frequency:
once daily (rivaroxaban, edoxaban) vs.
twice daily (apixaban, dabigatran)
Variable renal elimination
Renal considerations: highest renal elimination — dabigatran (~80%), edoxaban (~50%) — use with caution in renal impairment; dose adjustment or avoidance may be required.
Bleeding risk comparison: apixaban → lowest major bleeding risk; rivaroxaban and dabigatran → higher GI bleeding risk.
Situations where warfarin may be preferable to DOACs: severe renal impairment/kidney failure, severe liver impairment, significant history of GI disease, antiphospholipid syndrome, recurrent thrombosis while on a DOAC, significant adverse effects on a DOAC.
DOAC Dosing by Individual Drug
Apixaban (Eliquis) — Factor Xa Inhibitor
AFib: 5mg BID; reduce to 2.5mg BID if 2 of: age ≥80, weight ≤60kg, Cr ≥1.5mg/dL
DVT/PE treatment: 10mg BID × 7 days, then 5mg BID; recurrence-reduction dose 2.5mg BID after 6+ months of treatment
Half-life: 12 hours. Hepatic: no adjustment Child-Pugh A; not recommended Child-Pugh B/C
Not recommended as acute alternative to UFH in hemodynamically unstable PE
Dabigatran (Pradaxa) — Direct Thrombin Inhibitor
AFib: 150mg BID (renal-adjusted with P-gp inhibitors/CrCl thresholds)
DVT/PE treatment: 150mg BID (after 5–10 days parenteral lead-in)
Half-life: 12–17 hours. Avoid with rifampin; avoid P-gp inhibitors + CrCl <30
Do NOT chew/break/open capsules — moisture-sensitive; may cause dyspepsia
Rivaroxaban (Xarelto) — Factor Xa Inhibitor
AFib: 20mg once daily with evening meal (15mg if CrCl 15–50)
DVT/PE treatment: 15mg BID with food × 21 days, then 20mg daily with food × 6 months; reduce to 10mg daily after 6+ months for recurrence reduction
Half-life: 5–9 hours. Discontinue if acute renal failure develops on therapy
Edoxaban (Savaysa) — Factor Xa Inhibitor
AFib: 60mg daily; avoid if CrCl >95 (paradoxically less effective at very high clearance); 30mg daily if CrCl 15–50
DVT/PE treatment: 60mg daily after 5–10 days parenteral lead-in (30mg if ≤60kg)
Half-life: 10–14 hours. Avoid with rifampin
Betrixaban (Bevyxxa) — Factor Xa Inhibitor
Indication: VTE prophylaxis in acutely ill hospitalized adults — 160mg loading dose, then 80mg daily × 35–42 days
Half-life: 19–27 hours
Board trap: edoxaban is specifically avoided at CrCl >95 — a counterintuitive cutoff (normally we worry about renal impairment, not excellent renal function) tied to reduced efficacy at very high clearance rates in its pivotal trial.
DOAC Drug-Drug Interactions
| DOAC | Inducers (↓ effect) | Inhibitors (↑ effect/bleeding) |
|---|
| Apixaban | Avoid combined P-gp + strong CYP3A4 inducer | Reduce dose or avoid with combined P-gp + strong CYP3A4 inhibitors |
| Betrixaban | No data | Reduce dose with P-gp inhibitors |
| Dabigatran | Avoid with P-gp inducers | Evaluate P-gp inhibitors individually for dose adjustment/avoidance in renal impairment |
| Edoxaban | Avoid with rifampin | Reduce dose for DVT/PE treatment with select P-gp inhibitors |
| Rivaroxaban | Avoid combined P-gp + strong CYP3A4 inducer | Avoid with combined P-gp + strong CYP3A4 inhibitor |
P-Glycoprotein Inducers (examples)
Carbamazepine, dexamethasone, phenytoin, rifampicin, phenobarbital, clotrimazole, St. John's wort
CYP3A4 Inducers (examples)
Glucocorticosteroids, rifampicin, carbamazepine, phenobarbital, phenytoin
Pearl: notice carbamazepine, phenytoin, phenobarbital, and rifampicin appear as both P-gp AND CYP3A4 inducers — these "dual inducers" are the highest-risk drugs for DOAC treatment failure via reduced levels.
Anticoagulant Therapy Transitions
| Transition | General Rule |
|---|
| VKA → DOAC | Discontinue VKA; start DOAC once INR falls below drug-specific threshold (apixaban/dabigatran: INR <2.0; edoxaban: INR ≤2.5; rivaroxaban: INR <3.0) |
| DOAC → LMWH | Discontinue DOAC; start LMWH at time of next scheduled DOAC dose (dabigatran: 12h if CrCl ≥30, 24h if CrCl <30) |
| LMWH → DOAC | Discontinue LMWH; start DOAC 0–2 hours before (apixaban/rivaroxaban) or at time of next scheduled LMWH dose |
| DOAC → VKA | Overlap required — start parenteral anticoagulant + VKA concurrently at time of next DOAC dose, discontinue DOAC once INR is in range (varies by specific drug) |
Board trap: going TO a VKA from a DOAC requires overlap with a parenteral bridge (since VKA has delayed onset) — but going FROM a VKA to a DOAC requires waiting for the INR to fall below a threshold first (no overlap risk of double anticoagulation once DOAC starts fast).
Duration of Anticoagulation Therapy — ACCP Recommendations
| Indication | Preferred Agent | Duration |
|---|
| First proximal DVT/PE, reversible risk factor or surgery |
DOAC over VKA (2B), and over LMWH (2C) |
3 months recommended over shorter or extended therapy |
| First unprovoked proximal DVT/PE |
Same |
Low/moderate bleeding risk → extended (lifelong) preferred over 3 months; high bleeding risk → 3 months preferred; reassess bleeding risk annually |
| First distal DVT, reversible risk factor, no severe symptoms |
— |
Serial ultrasound surveillance × 2 weeks instead of anticoagulation; treat if extension occurs |
| Second unprovoked DVT/PE |
Switch to LMWH if recurrence on VKA/DOAC |
Extended (lifelong) if low/moderate bleeding risk; 3 months if high bleeding risk |
| Recurrent VTE on LMWH |
Increase LMWH dose by ¼ to ⅓ |
If can't increase intensity → consider IVC filter |
| Following completion, unprovoked proximal DVT/PE, patient declines continued anticoagulation |
Aspirin suggested over no aspirin |
Extended (lifelong) |
| Cancer-associated VTE |
LMWH over DOAC (2C) and over VKA (2B) — per this ACCP table; note more recent 2025 guidance favors DOAC first-line, see DOAC section |
Extended (lifelong) — grade 1B if low bleeding risk, 2B if high bleeding risk |
| Low-risk subsegmental PE, no proximal DVT |
— |
Surveillance over anticoagulation (2C); anticoagulate if higher recurrence risk |
Board trap — reconcile the two cancer-VTE recommendations: the ACCP table (older) says LMWH over DOAC for cancer-associated VTE, while newer 2025 guidance shifts to DOAC first-line even in cancer. On current boards, follow the most recent guidance (DOAC first-line) unless the question specifically references older ACCP grading — but recognize both exist in the literature.
Stroke Prevention in Atrial Fibrillation
- AFib is increasingly common in stroke patients and linked to higher mortality
- Stroke risk assessment: CHA₂DS₂-VASc (preferred) or CHADS₂
CHADS₂
C – CHF · H – Hypertension · A – Age ≥75 · D – Diabetes · S₂ – Prior stroke/TIA (2 points)
Score >1 → anticoagulation recommended
CHA₂DS₂-VASc
C – CHF · H – HTN · A₂ – Age ≥75 (2pts) · D – Diabetes · S₂ – Stroke/TIA (2pts) · V – Vascular disease · A – Age 65–74 · Sc – Female sex
More sensitive than CHADS₂ for low-risk patients
Anticoagulation thresholds: CHA₂DS₂-VASc ≥2 (men) or ≥3 (women) → anticoagulation recommended. Consider anticoagulation at score 1 (men) or 2 (women).
- DOACs preferred over warfarin UNLESS mechanical valve or moderate-severe mitral stenosis
- If INR control <70% time-in-range on warfarin → switch to DOAC
- DOACs vs. warfarin: ↓ stroke risk 21–35%; ↓ intracranial hemorrhage 33–60%
- In multimorbid patients: similar overall effectiveness; dabigatran → lower major bleeding vs. rivaroxaban; rivaroxaban → higher GI bleeding; DOACs → lower mortality vs. warfarin overall
Bleeding Risk Assessment
Essential before and during anticoagulation (both AFib and VTE). Multiple tools exist; predictive accuracy is variable.
ACCP VTE Bleeding Risk Factors
(e.g., advanced age, cancer, renal or hepatic failure)
Low risk: 0 risk factors ·
Moderate: 1 factor ·
High: ≥2 factors
HAS-BLED (for AFib)
H – HTN (SBP >160) · A – Abnormal renal/liver function · S – Stroke history · B – Bleeding history · L – Labile INR (if on warfarin) · E – Elderly (>65) · D – Drugs (antiplatelets/NSAIDs) or alcohol
Score ≥3 → high bleeding risk
Critical pearl: high stroke risk often overlaps with high bleeding risk — do NOT withhold anticoagulation solely because of bleeding risk in a high-stroke-risk patient. Reassess bleeding risk at every visit and address modifiable factors (alcohol, anemia, poor INR control, concomitant antiplatelet/NSAID use) instead of simply avoiding anticoagulation.
Management of Major Bleeding
Management depends on bleeding severity (major vs. nonmajor) and type of anticoagulant.
Major bleeding defined as: hemodynamic compromise, critical-site bleeding (e.g., intracranial), Hgb drop ≥2 g/dL, or transfusion of ≥2 units PRBCs.
Vitamin K Antagonists
Major bleeding: 4-factor PCC (Kcentra) + IV vitamin K + supportive care.
Kcentra preferred over FFP — faster, lower volume, better INR correction.
Nonmajor bleeding: hold warfarin ± vitamin K based on INR.
DOACs
Nonmajor bleeding: hold DOAC + local/supportive measures (leverages short ~12h half-life).
Major/life-threatening bleeding: use specific reversal agent (below).
Reversal Agents
- Dabigatran → Idarucizumab (Praxbind): rapid reversal (minutes), restores hemostasis; indicated for life-threatening bleeding or urgent procedures
- Factor Xa inhibitors (apixaban, rivaroxaban) → Andexanet alfa (Andexxa): effective hemostasis in ~79% of cases (ANNEXA-4 trial); risk of thrombosis ~18% → use with caution; limitations include cost and unclear optimal dosing/duration
- LMWH → Protamine sulfate (partial reversal)
Board trap: andexanet alfa's ~18% thrombosis risk is a critical, frequently tested safety caveat — it's not a "free" reversal; the post-reversal prothrombotic risk must be weighed, especially in a patient anticoagulated for a strong thrombotic indication.
Perioperative Management — Full Reference Tables
Table 1 — Bleeding Risk for Surgical Procedures
| High Risk | Low-to-Moderate Risk | Minimal Risk |
|---|
| Any operation >45 min; cardiac surgery; GI surgeries; intracranial/spinal surgery; kidney biopsy; major orthopedic surgery; major thoracic surgery; most cancer surgeries; most urologic surgeries; neuraxial anesthesia/epidural injections |
Abdominal hernia repair; abdominal hysterectomy; arthroscopy; bronchoscopy; colonoscopy; coronary angiography; GI endoscopy; hemorrhoidal surgery; laparoscopic cholecystectomy; lymph node biopsy |
Cataract surgery; minor dental procedures; minor dermatologic procedures; pacemaker/ICD implantation |
Rule of thumb: for minimal bleeding risk, antithrombotic medication can generally be continued. For low-to-moderate or high bleeding risk, most medications are stopped before surgery and restarted after.
Table 2 — Indications for Bridging When Holding Vitamin K Antagonists
| Risk Level | Mechanical Heart Valve | Atrial Fibrillation | Venous Thromboembolism |
|---|
High thrombotic risk
(>10%/yr arterial TE risk or >10%/month VTE risk) |
Any mechanical mitral valve; caged ball or tilting-disc aortic valve; stroke/TIA in past 3 months |
CHA₂DS₂-VASc ≥7; CHADS₂ 5 or 6; stroke/TIA in past 3 months; rheumatic valvular heart disease |
VTE in past 3 months; severe thrombophilia (protein C, protein S, or antithrombin deficiency, or antiphospholipid antibody syndrome); multiple thrombophilias; active cancer with high VTE risk |
Critical rule: heparin bridging is used ONLY for these high-thrombotic-risk conditions when holding a VKA. When holding a DOAC for a short period, bridging is generally NOT recommended (DOACs' rapid onset/offset makes it unnecessary).
Table 3 — Antithrombotic Medication Hold Time by Bleeding Risk
| Bleeding Risk | DOAC | Vitamin K Antagonist | Antiplatelet |
|---|
| High |
Hold 48h before surgery. Hold dabigatran 4 days if GFR <50. Consider longer hold for severe renal/hepatic impairment or CYP3A4 inhibitors. |
Hold 5 days before surgery. Bridge with heparin if thrombotic risk is high. |
Hold clopidogrel 5 days; ticagrelor 3–5 days; prasugrel 7–10 days. Continuing aspirin is recommended; if held, stop ≤7 days before. |
| Low-to-Moderate |
Hold 24h before surgery. Hold dabigatran 3 days if GFR <50. Consider longer hold for renal/hepatic impairment or CYP3A4 inhibitors. |
Hold 5 days before surgery. Bridge with heparin if thrombotic risk is high. |
Continue medication. |
| Minimal |
Continue medication. |
Continue medication. |
Continue medication. |
Board trap: even for low-to-moderate bleeding risk procedures, VKA is still held 5 days before surgery (same as high-risk) — the DOAC hold time scales with risk (24h vs. 48h), but the VKA hold time does NOT change between these two categories, reflecting warfarin's fixed ~5-day offset regardless of procedure risk.
Heparin Bridging — Practical Timing
- Can bridge with UFH or LMWH
- IV UFH: stop ≥4 hours before procedure; restart ≥24 hours after
- LMWH: give ½ dose 24 hours before procedure; restart ≥24 hours post-op
- If high bleeding risk: delay restart 48–72 hours to ensure hemostasis
DOAC Perioperative Restart
- Restart 24 hours post-op if bleeding risk is low
- Delay restart 48–72 hours if high bleeding risk surgery
- Rapid onset = risk of bleeding if restarted too early — always balance bleeding vs. thrombosis risk
- If restart is delayed, consider LMWH for VTE prophylaxis in the interim post-op period
Antiplatelet Perioperative Management
- Aspirin: continue for most noncardiac surgeries; if stopped, stop ≤7 days before
- Clopidogrel: stop 5 days before; ticagrelor: stop 3–5 days before; prasugrel: stop 7–10 days before
- Restart P2Y12 inhibitors within 24 hours post-op once hemostasis is achieved
- <12 weeks post-coronary stent: delay surgery or continue dual antiplatelet therapy (high thrombosis risk)
- >3 months post-stent: can stop the P2Y12 inhibitor, continue aspirin through surgery
- Bridging antiplatelet therapy is NOT recommended (no proven outcome benefit)
Table 4 — Day-by-Day Perioperative Timing Reference
| Day | DOACs | P2Y12 Inhibitors | Aspirin | VKA |
|---|
| −7 to −10 | NA | Stop prasugrel | Continue (or stop <7d prior) | NA |
| −5 | NA | Stop clopidogrel | — | Stop VKA |
| −4 | Stop dabigatran if high bleeding risk + GFR <50 | Stop ticagrelor (3–5 days) | — | No warfarin |
| −3 | Stop dabigatran if low-moderate risk + GFR <50 | Stop ticagrelor window continues | — | Start LMWH bridging if necessary; no warfarin |
| −2 | Stop DOAC if high bleeding risk + normal GFR | No prasugrel/clopidogrel/ticagrelor | — | Continue LMWH; no warfarin |
| −1 | Stop DOAC if low-moderate risk + normal GFR | No prasugrel/clopidogrel/ticagrelor | — | If bridging: give ½ daily LMWH dose 24h before, then stop LMWH; no warfarin |
| Surgery | No DOAC | No P2Y12 inhibitors | — | No LMWH; no warfarin |
| +1 | Restart DOAC if low-moderate bleeding risk | Restart all | — | Restart VKA |
| +2 | Restart DOAC if high bleeding risk | NA | — | Restart LMWH bridging (low-moderate risk) until INR at goal |
| +3 | NA | NA | — | Restart LMWH bridging (high bleeding risk) until INR at goal |